Preoperative Nivolumab in Patients With Locally Advanced Colon Cancer (T3 or T4): a Window-of-opportunity Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Tolerability and Safety
研究概览
简要总结
A monocentric window of opportunity study preceded by a safety run-in phase. The study population will include locally advanced colon patients (T3 or T4).
详细描述
An initial 6-patients safety run-in cohort will be followed by an expansion cohort, with a planned accrual of 16 patients.
Patients will receive nivolumab at a flat dosage of 240 mg every two weeks on Day -28 and Day-14 (+/- one day) prior to planned surgery on Day 0 or up to +7 days. Locally advanced colon cancer must be documented at screening (within 21 days prior to initiation of study treatment) and re-assessed prior surgery by spiral or multidetector computed tomography (CT) scan.
Postoperatively, standard adjuvant chemotherapy will be administered in pathological III-stage and at investigator discretion in pathological II-stage.
Safety Assessments: Toxicities will be evaluated throughout the study treatment and up to 30 days after surgery. Toxicity will be graded according to the NCI Common Toxicity Criteria.
The National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTC-AE) Version 4.03 will be used to evaluate the clinical safety of the treatment in this study. Patients will be assessed for AEs at each clinical visit and as necessary throughout the study. Grade ≥3 hematological and non-hematological toxicities will be recorded.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients diagnosed with histologically confirmed adenocarcinoma of colon with staging of locally advanced (T3 or T4)
- •No prior treatments (chemotherapy, radiation or surgery) for colon cancer
- •Either sex aged ≥ 18 years
- •Colon lesion determined and measured preoperatively by either spiral or multidetector CT scan
- •ECOG Performance Status ≤1 at study entry
- •Adequate bone marrow haematological function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L AND platelet count ≥ 100 x 109/L AND haemoglobin ≥ 9 g/dL
- •Adequate liver function: total bilirubin ≤ 1.5 x upper limit of normal (ULN) AND aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 X ULN
- •Adequate renal function: serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min in males and ≥50 mL/min in females (calculated according to Cockroft-Gault formula)
- •Serum calcium levels, international normalised ratio (INR) and partial thromboplastin time were within normal limits
- •Female subjects of childbearing potential must have a negative urine pregnancy test result at baseline and practice a reliable method of contraception throughout the study
- •Availability of tumor tissue from basal biopsy for immunoscore and biomarker analysis.
- •Ability to understand study-related patient information and provision of written informed consent for participation in the study
排除标准
- •Evidence of metastatic disease
- •Prior malignancy within the prior 5 years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- •Subjects with active, known or suspected autoimmune disease
- •Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment
- •Prior treatment with an anti-PD-1, anti-Programmed Death 1 ligand (PD-L1), anti-PD-L2, or anti-cytotoxic T lymphocyte associated antigen-4 (anti- CTLA-4) antibody
- •Female subjects who are pregnant (positive urine pregnancy test), breastfeeding, or who are of childbearing potential and not practicing a reliable method of birth control
- •Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study, or which would jeopardize compliance with the protocol, or would interfere with the results of the study
- •Patients with a history of cardiovascular or interstitial lung disease and evidence or risk of retinal vein occlusion or central serous retinopathy
- •Inability to regularly access center facilities for logistical or other reasons
- •History of poor co-operation, non-compliance with medical treatment, or unreliability
- •Participation in any interventional drug or medical device study within 30 days prior to treatment start
- •Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C (HCV antibody) with virus ribonucleic acid indicating acute or chronic infection;
- •Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
研究组 & 干预措施
Nivolumab
Patients will receive nivolumab at a flat dosage of 240 mg every two weeks on Day -28 and Day-14 (+/- one day) prior to planned surgery on Day 0 or up to +7 days
干预措施: Nivolumab (Drug)
结局指标
主要结局
Tolerability and Safety
时间窗: "up to 5 weeks"
To determine the feasibility of Nivolumab in the preoperative setting in patients with T3-T4 colon cancer: delay in surgery resection \> 21 days after last administration of nivolumab; severe adverse events-NCI CTC-AE Version 4.03 criteria
Clinical Activity
时间窗: "presurgery"
Objective Tumor Response Rate (ORR) as defined by Response Evaluation Criteria In Solid Tumors (RECIST)
Predictive Biomarkers
时间窗: "up to 10 weeks"
To determine molecular and immunophenotypic changes in tumor and peripheral blood evaluating several biomarkers. Since the identification of new markers for immunotherapy is rapidly evolving, the definitive list of analyses remains to be determined
次要结局
- Pathological Response("up to 6 weeks")
- Clinical efficacy(5 years)
- Toxicities("up to 3 months")
- Metabolic Response("presurgery")